β-Actin-dependent global chromatin organization and gene expression programs control cellular identity

Xin Xie, Bader Almuzzaini, Nizar Drou, Stephan Kremb, Ayman Yousif, Ann Kristin Östlund Farrants, Kristin Gunsalus, Piergiorgio Percipalle

Research output: Contribution to journalArticle

Abstract

During differentiation and development, cell fate and identity are established by waves of genetic reprogramming. Although the mechanisms are largely unknown, during these events, dynamic chromatin reorganization is likely to ensure that multiple genes involved in the same cellular functions are coregulated, depending on the nuclear environment. In this study, using high-content screening of embryonic fibroblasts froma β-actin knockout (KO) mouse, we found major chromatin rearrangements and changes in histone modifications, such asmethylatedhistone (H)3-lysine-(K)9.Genome-wideH3K9 trimethylation-(Me)3 landscape changes correlate with gene up- and down-regulation in β-actinKOcells.Mechanistically, we found loss of chromatin association by the Brahma-related gene (Brg)/Brahma-associated factor (BAF) chromatin remodeling complex subunit Brg1 in the absence of β-actin. This actin-dependent chromatin reorganization was concomitant with the up-regulation of sets of genes involved in angiogenesis, cytoskeletal organization, andmyofibroblast features in β-actin KO cells. Some of these genes and phenotypeswere gained inaβ-actin dose-dependentmanner.Moreover, reintroducing anuclear localization signal-containing β-actin in the knockout cells affected nuclear features and gene expression. Our results suggest that, by affecting the genome-wide organization of heterochromatin through the chromatin-binding activity of the BAF complex, β-actin plays an essential role in the determination of gene expression programs and cellular identity.

Original languageEnglish (US)
Pages (from-to)1296-1314
Number of pages19
JournalFASEB Journal
Volume32
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • Chromatin
  • Epigenetics
  • Genome-wide analysis
  • Genomic reprogramming
  • Nuclear actin

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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